AI Article Synopsis

  • Researchers isolated a new group of polyhydroxylated steroids, named theonellasterols and conicasterols, from a marine sponge using chromatography and HPLC purification.
  • The structures of these compounds were determined through advanced spectroscopic techniques, and their ability to interact with nuclear receptors was explored using docking calculations.
  • Theonellasterol G was identified as a significant modulator of nuclear receptors, showing the potential to influence liver disease treatment by inducing and regulating specific genes in liver cells.

Article Abstract

Silica gel column chromatography, followed by HPLC purification on the apolar fraction of the methanol extract of marine sponge Theonella swinhoei, resulted in the isolation of a library of 10 polyhydroxylated steroids which we named theonellasterols B-H (1-7) and conicasterols B-D (8-10). The structures were determined on the basis of extensive spectroscopic data (MS, (1)H and (13)C NMR, COSY, HSQC, HMBC, and ROESY) analysis, and the putative binding mode to nuclear receptors (NRs) has been obtained through docking calculations. Pharmacological and structure-activity relationship analysis demonstrate that these natural polyhydroxylated steroids are potent ligands of human nuclear pregnane receptor (PXR) and modulator of farnesoid-X-receptor (FXR). In addition, the molecular characterization of theonellasterol G allowed the identification of the first FXR modulator and PXR ligand so far identified. Exposure of liver cells to this agent resulted in potent induction of PXR-regulated genes and modulation of FXR-regulated genes, highlighting its pharmacological potential in the treatment of liver disorders.

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http://dx.doi.org/10.1021/jm200169tDOI Listing

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